补肾抗衰片对实验性动脉粥样硬化家兔的NF-κB及炎症因子的影响

Effect of Bushen Kangshuai Tablet on NF-κB Signal Pathway and Inflammation Factors in Rabbits with Experimental Atherosclerosis

目的探讨补肾抗衰片对家兔动脉粥样硬化的干预作用及作用机制。方法36只日本雄性大耳白兔随机分为4组:正常对照组6只,模型组10只,补肾抗衰组10只,辛伐他汀组10只。正常对照组饲喂普通饲料;模型组和给药组通过高脂饲料(第1周至第10周)、免疫损伤(第2周)结合经股动脉球囊拉伤(第4周)建立动脉粥样硬化家兔模型,另外补肾抗衰组及辛伐他汀组从第1周开始分别加喂补肾抗衰片和辛伐他汀片,直至第10周取材。于实验开始时(0周)及3、6、10周时测定各组胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、白介素-1(IL-1)、单核细胞趋化因子(MCP-1)、肿瘤坏死因子(TNF-α)及10周时主动脉壁细胞核因子(NF-κB)的表达,病理检测主动脉斑块与内膜面积比(PA/IA)、内膜厚度(IT)、内膜增生指数(IHI)。并对血脂、炎症细胞因子及IHI进行相关性分析。结果与正常对照组比较,各时间点模型组血脂水平及炎症因子水平显著增高(P<0.01),主动脉斑块与内膜面积比、内膜与中膜厚度比及内膜增生指数均有不同程度升高(P<0.01)。两给药组各时间点的血清IL-1、MCP-1、TNF-α及动脉壁NF-κB表达,以及斑块与内膜面积比、内膜中膜厚度比及内膜增生指数均有不同程度的降低(P<0.05,P<0.01)。Pearson相关性分析表明模型组TC与IL-1、TNF-α与IHI呈正相关,补肾组TC与IHI、IL-1与IHI、TNF-α与IHI、TNF-α与IL-1均呈正相关,血脂与炎症细胞因子之间无相关性(P>0.05)。结论补肾抗衰片可抑制动脉粥样硬化家兔模型的炎症反应,抗动脉粥样硬化形成,且作用和血脂水平无直接的相关性。

Objective To observe the intervening effect and acting mechanism of Bushen Kangshuai Tablet（BKT） on rabbits′ atherosclerosis（AS）.Methods Thirty-six white Japanese rabbits were randomly divided into four groups： 6 in the normal control group,and each 10 in the model group,the BKT group and the simvastatin group.The AS model was established by high fatty diet feeding from the 1st to the 10th week,combined with immune injury at the 2nd week and femoral arterial balloon tearing at the 4th week.The medication of BKT and simvastatin was given during the whole 10-week course.Levels of triglyceride（TG）,total cholesterol（TC）,low-density lipoprotein cholesterol（LDL-C）,high-density lipoprotein cholesterol（HDL-C）,interleukin-1（IL-1）,monocyte chemotactic protein-1（MCP-1）,and tumor necrosis factor-α（TNF-α） were measured at the beginning and the 3rd,6th and 10th weekend of the experiment.The nuclear factor-kappa B（NF-κB） expression in the aortic wall,ratio of plaque area to intima area（PA/IA）,intima thickness（IT）,aortic intima/media thickness ratio（IT/MT） and intima hyperplasia index（IHI） were measured at the terminal of the experiment.The correlation analysis was conducted between serum lipids,inflammation factors and IHI.Results Compared with the normal control group,all indices of the blood lipids and inflammation factors measured at various time points,and the PA/IA,IT/MT ratios as well as IHI in the model group were higher（P〈0.01,P〈0.05）.Compared with the model group,the levels of IL-1,MCP-1,TNF-α,NF-κB as well as the ratios of PA/IA,IT/MT and IHI were lower in the two treated groups at all time points after treatment（P〈0.01 or P〈0.05）.Pearson correlation analysis showed positive correlation between TC with IL-1,and TNF-α with IHI in the model group（P〈0.05）;also between TC with IHI,IL-1 with IHI,and TNF-α with IHI and IL-1 in the BKT group（P〈0.05）,while no correlation between blood lipids with inflammation factors was observed.Conclusion BKT could suppress the inflammation reaction in rabbits to prevent AS formation,the action is not directly correlated with the blood lipid level.